Cytokine upregulation in tubulointerstitial nephritis associated with membranous nephropathy

Abstract

tubulointerstitial nephritis models.2,3 However, the crucial role of cytokines has not been fully investigated in the pathogenesis of human tubulointerstitial nephritis. Here we describe a patient who developed tubulointerstitial nephritis associated with membranous nephropathy showing the upregulation of cytokines. This suggests that dysregulation of cytokines may be involved in the pathogenesis of human tubulointerstitial nephritis. Case reportIn May 1990, a 45-year-old woman was admitted to Kanazawa University Hospital for evaluation of insidious edema and proteinuria of several months' duration. She denied any history of drug usage or past history of diseases including urinary abnormalities. Physical examination revealed edema of the face and bilateral lower legs. Urine analysis showed proteinuria of 15.0 g/day and no microscopic hematuria. Urine sediment showed clustering of leukocytes and some hyaline casts. Urine culture and cytology were negative. Hematological laboratory test results were: hematocrit, 30.7%; red blood count, 3 310 000/mm 3 ; and hemoglobin, 10.4 g/dl. Renal function was mildly reduced (24-h creatinine clearance (Ccr) 80.6 ml/min), while urinary 2-microglobulin and N-acetyl-glucosaminidase showed high levels (20 000 ng/ml and 471.1 IU/l, respectively). Total serum protein was 4.3 g/dl (albumin 1.7 g/dl) and serum cholesterol was high (340 mg/dl). There was marked IgG hypogammaglobulinemia (628 mg/dl). Results of serological testing for antinuclear antibody or components of complement were negative or normal. In addition, there were no clinical symptoms suggestive of collagen diseases.Renal biopsy showed mild diffuse thickening of the glomerular capillary walls accompanied by spike formation. The interstitium was diffusely infiltrated by small round cells, and tubulitis was detected (Fig. 1). Immunofluorescence microscopy revealed granular deposition of immune complex containing IgG and C3 along the glomerular capillary walls. Subepithelial dense deposits were also observed Abstract We describe the upregulation of cytokines in a 45-year-old woman with tubulointerstitial nephritis and membranous nephropathy revealed by renal biopsy. She was treated with a combination of prednisolone and cyclosporin. Histological findings showed appreciable improvement, and urinary protein excretion was decreased from 15 g/day to 1 g/day. Elevated urinary levels of chemokines, interleukin (IL)-8 and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1, and serum levels of tumor necrosis factor (TNF)-α decreased during convalescence; 13 other patients with membranous nephropathy did not show elevation of these cytokines. These results suggest that the upregulation of these cytokines may participate in the pathogenesis of tubulointerstitial nephritis and that combination therapy of prednisolone and cyclosporin may be effective, possibly via inducing a decrease in these cytokines.

Chemokines in renal diseases

“…Although, the intervention of fractalkine receptor, CX3CR1 showed the prevention of glomerular damage with the decrease in leukocyte infiltration (42), the blockade of fractalkine/its receptor may be beneficial to the prevention of interstitial damage as well as glomerular diseases. In addition, MCP-1, as anticipated, was involved in the interstitial nephritis (43). MCP-1 and other C-C chemokines were involved in the pathogenesis of allograft rejection (44).…”